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ISSN 2347-6893

Developmental Adipokines and Maternal Obesity Interactions

R.G. Ahmed
Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Beni-Suef University, BeniSuef, Egypt
Email: Tel. number: 002-010-9147-1828

Adipokines are involved in the developmental programming during fetal development and early life, and might
contribute to pregnancy complications. Maternal obesity has an impact on intrauterine fetal life that extends to abnormal
changes in the adipose tissue and metabolic disorders in the newborns and even adulthood. This overview discusses the
potential importance of adipokines during gestational diabetes mellitus (GDM) and in fetal metabolic programming.
Various adipokines secreted from fat tissue as the key players in reprogramming maternal physiology to achieve an
insulin-resistant state during pregnancy, especially when complicated by GDM. Indeed, this review hypothesized that the
disturbance in adipokines may be associated with GDM in pregnant obese women or animals. This may influence,
generally, on the health of the embryos, newborns and adulthood depending on proinflammatory markers. Finally, the
obesity of mothers and disturbance in adipokines prior to pregnancy are a significant risk factor for the disturbed
development of the pregnancy and the child, and develop metabolic syndrome. However, there are obvious species
differences between pregnant women and animal models. Thus, maintaining normoglycaemia and adipokines levels
during pregnancy may play an important role in a healthy life for the newborns.

Key words: Adipokines; obesity; mothers; development; offspring.

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I- Introduction
Obesity is powerfully linked with changes in the physiological function of adipose tissue, leading to
insulin resistance, chronic inflammation, and altered secretion of adipokines (Bljaji et al., 2014; Prior et al.,
2014; Ramirez et al., 2014). Indeed, adipose tissue dysfunction might play a critical role in the different
obesity linked diseases including inflammation, insulin resistance and cancer. White adipose tissue (WAT) is a
complex and metabolically active organ, with a relevant vital role in regulating whole-body metabolism (Houde
et al., 2013). WAT is the largest energy storage organ, having an essential lipid storing capacity in periods
when energy input exceeds energy expenditure and with a lipolytic function during energy deprivation (Jenum
et al., 2013; Loy and Hamid Jan, 2014). In addition to its primary role as a fuel reservoir, WAT has been
confirmed as a principal endocrine organ, since the tissue synthesizes and secretes an array of sex steroids,
and bioactive peptides termed adipokines, involved in the physiological regulation of fat storage, energy
metabolism, food intake, insulin sensitivity, and immune function among others (Khalyfa et al., 2013). In this
section, I summarized the general biological function of adipose tissue in table (1) and figure (1), and I
compared between the secretion and action of potentially beneficial adipokines (leptin, adiponectin, apelin and
visfatin) linking to obesity in table (2).

II- Summary about the different states of adiponectinaemia (Table 3).

III- Summary about the adipokines & insulin resistance interactions (figure 2).
IV- Role of inflammation in pathogenesis of insulin resistance, obesity and
cardiovascular diseases (Table 4):
Increased adipose tissue mass that is linked with obesity and cardiovascular disease has been
associated with a low-grade, chronic inflammatory response that is characterized by altered production of
adipokines and increased markers of inflammation, such as TNF- and IL6 (Stupin and Arabin, 2014) or
MCP-1 (Harwood Jr, 2012). Over-stimulation of inflammatory pathways in insulin-sensitive tissues provides
rise to local and systemic insulin resistance (Cai et al., 2005). Markers of systemic inflammation in humans
are strongly connected with insulin resistance (de Rooij et al., 2009) and predict the development of diabetes
type two (T2DM) (Ahmed, 2011; Miehle et al., 2012). Infact, acute TNF- infusion induces skeletal muscle
insulin resistance in humans (Plomgaard et al., 2005), while both acute and chronic MCP-1 infusion stimulates
insulin resistance in rodents (Kalupahana et al., 2012). Notably, adipose tissue cells from the stromal vascular
fraction, and in particular resident macrophages, are responsible for the chronic inflammatory responses
recorded in obesity (Weisberg et al., 2003). These resident macrophages vary in their properties depending
on whether they are contained in lean or fat-laden adipose tissue (Harwood Jr, 2012). For example,
macrophages residing in lean adipose tissue are illustrated by increased expression of anti-inflammatory
cytokines, such as interleukin 10 (IL-10), explain an increased capacity for tissue repair and angiogenesis,
and are frequently referred to as M2, or alternatively-activated macrophages (Lumeng et al., 2007). However,
expansion of adipose tissue in obesity is linked with an increased infiltration by circulating macrophages of the
M1, or classically-activated, phenotype (Coenen et al., 2007). These macrophages are characteristically
recruited to sites of tissue damage and are in a pro-inflammatory state with increased expression of
proinflammatory cytokines, such as TNF- and IL6, that can exert strong paracrine effects on a variety of
adipose tissue functions (Lumeng et al., 2007). The local effects of proinflammatory cytokines on adipose
tissue lipolysis may contribute to the development of insulin resistance by promoting the liberate of fatty acids
from adipose tissue into the circulation, which may then lead to lipid accumulation and insulin resistance in
other tissues such as skeletal muscle and liver (Goossens, 2008). Furthermore, reduced adiponectin
concentrations may have harmful effects on fat oxidation, since it has been demonstrated that adiponectin
increases fat oxidation via activation of AMP-activated protein kinase in rat skeletal muscle and myocytes
(C2C12) (Yamauchi et al., 2002). Interestingly, in humans, low adiponectin serum levels at baseline
independently predict future risk to develop T2DM (Spranger et al., 2003) and coronary artery disease
(Fasshauer et al., 2004) and high plasma adiponectin predicts a lower risk of future myocardial infarction
(Pischon et al., 2004). I summarized the different states for adiponectinaemia in table 3. It is obvious from
these studies that there are linking between insulin receptor signaling and inflammatory pathways (Hirosumi et
al., 2002). Generally, the detailed of pro-inflammatory cytokines and chemokines during obesity are discussed
in table 4.

V- Adipokines, maternal obesity and development (figure 3):

Gestation is a stage that results in increased adipocyte volume, and it is recognized that adipose fat
depots are the net balance of synthesis and hydrolysis of triacylglycerols via lipogenesis and lipolysis (Ramos
et al., 2003). Also, several adipokines such as leptin (LEP; OMIM 164160), adiponectin (ApN; OMIM 605441),

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resistin (RETN; OMIM 605565) and inflammatory cytokines [tumor necrosis factor- (TNF-; OMIM 191160),
and interleukin-6 (IL-6; OMIM 147620)], and chemokines [interleukin-8 (IL-8; OMIM 146930)] have been
suggested as much stronger predictors of pregnancy-linked insulin resistance than gestational hormones,
including human placental lactogen and steroids (Radaelli et al., 2003; Taylor et al., 2014). Recently,
adiponectin secretion and adiponectin mRNA levels in WAT decline with the gestation progress suggesting
that there are pregnancy-associated factors that reduce adiponectin levels (Catalano et al., 2006). In addition,
in humans, the developing placenta expresses both leptin and its receptor, and placental resistin (ZavalzaGmez et al., 2008). Their levels correlate with the condition of reduced insulin sensitivity often developed in
the latter stages of pregnancy, thus contributing to successful development of the fetus (Cortelazzi et al.,
2007). Furthermore, the human placenta has been found to express nearly all known cytokines. Increasing
adiposity is associated with the secretion of proinflammatory cytokines from adipose tissue, suggesting that
these cytokines may play an essential role in fuel availability during pregnancy (Lyon et al., 2003). Moreover,
cytokine production is related to pathologic risk and to delivery mode itself (Malamitsi-Puchner et al., 2005).
There have been only a few papers demonstrating cytokine profiles, including many kinds of cytokines in cord
blood (Takahashi et al., 2010). IL-6 is a useful marker for a systemic fetal inflammatory response (Gomez et
al., 1998). Also, the levels of IL-8, MCP-1 and MIP-1b were increased in preterm birth (Matoba et al., 2009)
and serum levels of IL-8 and MCP-1 in cord blood significantly associated with gestational ages (Takahashi et
al., 2010). However, IL-4 and IL-13 did not cross the placenta in measurable amounts (Lim et al., 2009). In
previous investigations, circulating levels of leptin, adiponectin and TNF- in the early pregnancy strongly
predicted the development of GDM (Gao et al., 2008). Also, GDM elicits main variations in the expression
profile of placental genes with a prominent increase in markers and mediators of inflammation (Radaelli et al.,
Previous studies have reported a connection between childhood maltreatment and adulthood obesity
(Midei et al., 2010). Obesity is also associated with lowered serum adiponectin levels which reflect a disturbed
inflammatory state during childhood (Gustafson, 2010). Adiponectin inhibits the functions of TNF- which
associated with post-traumatic stress disorder (Gustafson, 2010) and inhibits the secretion of several other
pro-inflammatory cytokines from endothelial cells (Gustafson, 2010). This can increase the childhood
vulnerability to depression and permanent hyperactivity of the sympathetic nervous system, as well as a
variety of conditions linked to disturbed inflammatory systems (Charmandari et al., 2003). Based on these
observations, placental-derived hormones are supposed to be a main factor in reprogramming maternal
physiology to achieve an insulin-resistant state. However, more studies are essential about this issue.

VI- Future directions

- Discover the ranges of several adipokines serum levels at which obesity-related disorders are
observed with high frequency. These measurements could therefore be used as a biologic marker and/or
pharmacologic agent in the management of obesity, inflammatory, metabolic, and cardiovascular disorders.
- Determine the complex nature of several adipokines signaling and their specific roles during pregnancy.

VII- Conflict of Interest: There is no conflict of interest.

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IX- Legends
- Table legends:
Table 1: Summary about the biological function of adipose tissue.
Table 2. General action of leptin, adiponectin, apelin and visfatin linking to obesity.
Table 3. Summary about the different states of adiponectinae.
Table 4. Pro-inflammatory cytokines and chemokines during obesity.

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- Figure legends:
Figure 1. General adipokines network.
Figure 2. Adipokines and insulin resistance interactions.
Figure 3. Adipokines, maternal obesity and development.

X- Abbreviations
ApN, adiponectin;
ApoE, apoliproprotein E;
ASP, acylation-stimulating protein;
AT, adipose tissue;
BAT, brown adipose tissue;
BBB, bloodbrain barrier;
BMI, body mass index;
CETP, cholesterol ester transfer protein;
CRP, C-reactive protein;
CVD, cardiovascular disease;
ER, endoplasmic reticulum;
FABPs, fatty-acid-binding proteins;
FFA, free fatty acid;
GDM, gestational diabetes mellitus;
HMW, high molecular weight;
IGF-1, insulin like growth factor-1;
IL-6,8,10, interleukin-6,8,10;
LEP, leptin;
LPL, lipoprotein lipase;
MCP-1, monocyte chemo-attractant protein-1;
MIF, macrophage migration inhibitory factor;
NF-B, nuclear factor kappa-light-chain-enhancer of activated B-cells;
NGF, nerve growth factor;
PAI-1, platelet (plasminogen) activator inhibitor-1;
RBP4, retinol binding protein-4;
RETN, resistin;
SAA, serum amyloid A;
Sc, Subcutaneous;
SVC, stromal-vascular cells;
T2DM, diabetes type two;
TGF-, transforming growth factor-;
TNF- , tumor necrosis factor- ;
TNF-, tumor necrosis factor-;
VEGF, vascular endothelial growth factor;
WAT, White adipose tissue;

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Table 1. Summary about the biological function of adipose tissue.
Compare face

- Appetite and energy balance

Increase food intake


Increase food







- Adipogenesis
- Metabolic functions
- Immune modulator
- Inflammatory responses
- Secretory functions

- Appetite and energy balance

- Glucose homeostasis
- Fatty acid catabolism
- Adipogenesis
- Secretory functions
- Strong anti-inflammatory function
- Promotes the phagocytosis of apoptotic cells
- A potent antiatherogenic factor
- Specific marker for insulin sensitivity and
metabolic processes


- Insulin resistance
- Metabolic functions


-Insulin secretion
- Specific marker for insulin sensitivity and
metabolic processes


- Blood pressure
- Modulation of food intake.
- Specific marker for insulin sensitivity and
metabolic processes


- Specific marker for insulin sensitivity and

metabolic processes


- Insulin resistance
- Increases insulin resistance


- Insulin sensitivity and control of carbohydrate

storage and oxidation.


- They are cytokines

IL-6, -8

- Inflammation
- Adipogenesis
- Metabolic functions
- Secretory functions


proinflammatory agents such as lipopolysaccharide
(LPS) and TNF-


- It is cytokine

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- Adipogenesis

-Stimulates triglyceride storage in adipocytes;

activates alternate complement pathway


- Believed to enhance the actions of insulin




- Stimulates angiogenesis (vascular proliferation)

in white adipose tissue




- It is neurotrophins


- Inhibits




- Haemostatic and haemodynamic factor


- Family of carrier proteins for fatty acids and

other lipophilic substances such as eicosanoids
and retinoids.
- These proteins are thought to facilitate the
transfer of fatty acids between extra- and intracellular membranes.



- Haemostatic and haemodynamic factor

- Regulates preadipocyte proliferation
differentiation and also adipocyte apoptosis


- It is chemokine.
- Immunoregulator with paracrine actions in white
adipose tissue


- It is chemokine.
- Recruits monocytes to sites of injury and


- Hydrolyzes triglycerides in triglyceride-rich

lipoproteins allowing cellular uptake


- Stimulates proliferation and differentiation of








- Stimulates triglyceride synthesis in white adipose

tissue; antilipolytic




Tissue factor

- Initiates the coagulation cascade


- They are acute phase proteins



- Anti-inflammatory


Adapted from Otero et al. (2003), Kadowaki & Yamauchi (2005), Tilg and Wolf (2005), Ahima (2006), Ronti et al. (2006),
Fonseca-Alaniz et al. (2007), Takemura et al. (2007), Hajer et al. (2008), Vzquez-Vela et al (2008), Zou & Shao (2008),
Lagol et al. (2009), German et al. (2010), Karastergiou & Mohamed-Ali (2010), Cekmez et al. (2011) and Harwood Jr
(2012). ApN, adiponectin; ApoE, apoliproprotein E; ASP, acylation-stimulating protein; CETP, cholesterol ester transfer
protein; CRP, C-reactive protein; FABPs, fatty-acid-binding proteins; FFA, free fatty acid; IGF-1, insulin like growth factor1; IL-6,8,10, interleukin-6,8,10; LPL, lipoprotein lipase; MCP-1, monocyte chemo-attractant protein-1; MIF, macrophage
migration inhibitory factor; NGF, nerve growth factor; PAI-1, platelet (plasminogen) activator inhibitor-1; RBP4, retinol

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binding protein-4; SAA, serum amyloid A; TGF-, transforming growth factor-; TNF-, tumor necrosis factor-; TNF- ,
tumor necrosis factor- ; VEGF, vascular endothelial growth factor.

Secreted proteins without hormonal actions.

Table 2. General action of leptin, adiponectin, apelin and visfatin linking to obesity.


Adiponectin (ApN)




- It is a 16-kDa hormone produced

by adipocytes and virtually
undetectable in the stromalvascular cells fraction of adipose
tissue. Its expression is restricted
to mature fat cells in man (Halleux
et al., 2001).

- It is a 30-kDa protein
adipose tissue (Maeda et al.,
1996; Scherer et al., 1995). It
found in the blood stream in
three forms: trimer, hexamer
and high molecular weight
(HMW) 12- to 18-mer ApN
(Kadowaki et al., 2006).

ligand for the
orphan G-protein
coupled receptor,
AJP, which is the
closest homolog
to angiotensin II
receptor (Japp et
al., 2008). It is
present in several
tissues, in the
bloodstream and
(AT) (Cekmez et
al., 2011).

- It is as a
protein involved
in immune B-cell
maturation (preB
(Samal et al.,
1994) and with
(Fukuhara et al.,
2005). It found in
visceral AT, from
which the name
(Fukuhara et al.,




Not reported


oxidation in
(Emilsson et
al., 1997).

- Increase energy

Not reported

energy storage in
Matheny, 1998).

Matheny, 1998)
and apoptosis of
adipocytes (Lago
et al., 2009).

- Decrease
in liver and
(Emilsson et
Carbone et
al., 2012).

- Decrease fatty
(Takekoshi et al.,


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- Increase levels
of GLUT-4 in
synthesis in liver,
glucose uptake in
BAT (Qian et al.,
1998) and insulin
sensitivity (Bai et


sensitivity in
(Emilsson et
and levels of

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al., 1996).
- Decrease levels
of GLUT-4 in
WAT (Qian et al.,
pancreatic islets
(Kamohara et al.,
1997; Carbone et
al., 2012).

- Central action:
It represents a signal to the brain
(e.g., hypothalamus, cortex and
limbic areas) to inhibit food intake
and reduce weight (Zhang et al.,
1994) because of humans and
rodents lacking a functional leptin
feeding and obesity (Hajer et al.,
2008). The vital action of leptin in
the hypothalamus has been best
described with regards to energy
homeostasis and reproductive
functions (Badman and Flier,
2007). Additionally to its action on
the hypothalamus, leptin may also
act on the cortex and limbic areas,
which are regulated the cognitive
and emotional feeding behavior
(Farooqi et al., 2007; Rosenbaum
et al., 2008). As predictable, leptin
treatment successfully reversed
the obesity and leptin resistance
(Ahima, 2008).
Currently, leptin represents as a
hormone responsible for signaling
energy deficiency rather than a
signal to lose weight (Badman
and Flier, 2007; Kershaw and
Flier, 2004).

muscle (Berg
et al., 2001).
- Decrease
production in
(Yamauchi et
al., 2001 &

adipokines, circulating ApN is
negatively associated with the
body mass index (BMI) (Arita
et al., 1999; Brichard et al.,
2003) and decreased in obese
subjects, in type 2 diabetes or
cardiovascular disease (CVD)
(Ouchi and Walsh, 2007). This
sub-regulation may involve the
abnormal hormonal milieu
(Delporte et al., 2002; Halleux
et al., 2001), together with the
enhanced oxidative stress
(Furukawa et al., 2004) and
the pro-inflammatory state
(Bruun et al., 2003) that exist
in obesity and the metabolic

- AT apelin and
(Heinonen et al.,
Conversely, both
circulating apelin
expression in AT
after weight loss
consecutive to a
hypocaloric diet
in obese women
(Castan-Laurell et
al., 2008). Its
expression was
(sc) tissue and
there was no
adipocyte apelin
and sc fat pads in
mice (Boucher et
al., 2005).

obesity and type
2 diabetes have
been found in
some but not all
studies (Garten
et al., 2009;
Kern, 2008); the
findings may be
due in part to
(Garten et al.,

AdipoR1 and AdipoR2 serve

as main receptors for ApN in
vivo and belong to a new
family of receptors (seven
transmembrane domains) but

- It promising
management of
insulin resistance
(Cekmez et al.,

- It has vital roles

(Cekmez et al.,

- Peripheral action:
It has actions in a number of
peripheral tissues (e.g., cells of
the pancreas, liver and immune
Mohamed-Ali, 2010). Moreover,
disruption of peripheral leptin
signaling in mice caused no
significant variation in energy
balance or glucose homeostasis
(Guo et al., 2007).
& effects

Leptin from the periphery is

combines with its receptor b in the
hypothalamus, and stimulates
JAK-STAT3, leading to repression
of orexigenic peptides (e.g.,

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neuropeptide Y and agouti-related
anorexigenic peptides (e.g.,
corticotrophin-releasing hormone)
(Ahima, 2008), in that way
curtailing food intake. In the
resistance to leptin has been
ascribed to reduced transport of
leptin across the bloodbrain
barrier (BBB) and to increased
hypothalamic levels of SOCS3
and endoplasmic reticulum (ER)
signaling (Flier, 1998; Morton et
al., 2005; Ozcan et al., 2009).
Notably, low leptin levels stimulate
overfeeding and repress energy
immunity (Maury and Brichard,

functionally distinct from Gprotein coupled receptors

(Maury and Brichard, 2010).
AdipoR1 is expressed in
muscle, while AdipoR2 is
expressed in liver (Yamauchi
et al., 2003). AdipoR1 is more
tightly associated to the
activation of AMPK pathways
that adjust the inhibition of
gluconeogenesis together with
increased fatty acid oxidation,
while AdipoR2 is more
concerned with the activation
of the PPAR- pathways,
dissipation by increasing fatty
acid oxidation and reduce
inflammation (Capeau, 2007;
Yamauchi et al., 2007).
Interaction of an adaptor
protein, APPL1 with AdipoR1
appears to play significant
roles in ApN signaling (Mao et
al., 2006). After binding, ApN
showed insulin-sensitizing and
fat-burning effects suggestive
of those of leptin, but
possesses anti-atherogenic,
anti-inflammatory and antioxidant properties as well,
simultaneously several facets
of the metabolic syndrome
(Kadowaki and Yamauchi,
2005; Takemura et al., 2007).


Table 3. Summary about the different states of adiponectinae

Compare face




Raised levels of these endogenous cytokines,

particularly several pro-inflammatory cytokines
such as IL-6, IL-8 and TNF-a (Engeli et al.,
2003) may be directly responsible for the
inhibition of adiponectin secretion (Bruun et al.,
2001; German et al., 2010).

Loss of insulin receptor (dysfunction) could

be construed as a compensatory response
of the adipose tissue that exerts insulinsensitising effects on remote tissues
(Semple et al., 2006 & 2007).


In experimental models, adiponectin has been

reported to have anti-inflammatory effects
against liver injury (Lago et al., 2007).
Adiponectin administration recovers liver
function in both alcoholic and non-alcoholic
fatty liver disease as the result of TNF
suppression, and in mice it reduces liver
enzyme levels, hepatomegaly and steatosis
(Xu et al., 2003), attenuates liver fibrosis
(Kamada et al., 2003), and protects against
LPS-induced liver injury (Masaki et al., 2004).

In mice, expressing the insulin receptor only

in adipose tissue, brain and pancreatic beta
cells, increased adiponectin coexists with
adiponectin resistance, as obvious by
blunted ability of adiponectin to lower blood
glucose and stimulate hepatic AMPdependent kinase phosphorylation (Lin et
al., 2007).

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In humans, hypoadiponectinaemia have been

(Funahashi et al., 1999), and they are
associated with increased vascular smooth cell
proliferation in response to injury, increased
free fatty acid levels, and insulin resistance
(Pischon et al., 2004). The conjunction of prodiabetic and proatherogenic effects of reduced
adiponectin levels, as observed in metabolic
syndrome, make adiponectin a bridge between
obesity and inflammation (Lago et al., 2007).
Also, plasma adiponectin levels are reduced in
subjects with obesity and insulin resistance or
type 2 diabetes mellitus, and are inversely
correlated with visfatin and fasting insulin
levels (Weyer et al., 2001; Punthakee et al.,
2006; Cekmez et al., 2011).

concentrations correlate
with insulin
sensitivity, and yet in patients with severe
insulin resistance due to loss of insulin
receptor function (Groeneveld et al., 2012).
This mechanism remains to be fully

Table 4. Pro-inflammatory cytokines and chemokines during obesity


Tumor necrosis factor-alpha

(TNF- )

Monocyte chemoattractant



- It is an immunomodulatory and
pro-inflammatory cytokine that is
synthesized as a 26 kDa
metalloproteinases and is released
into the circulation as a soluble
molecule (Kriegler et al., 1988;
Zhuang et al., 2009).

- It is a chemokine (C-C motif),

member of the small inducible
cytokine family and ligand 2 (CCL2) (Kim et al., 2006; Goossens,

- It is a cytokine produced by
several cells (fibroblasts,
endothelial cells, monocytes,
adipocytes, etc) (Bastard et
al., 2007).


- It is produced in the stroma of fat

tissue, mainly in macrophage
Weisberg et al., 2003; Winkler et
al., 2003; Park et al., 2005; Cao et
al., 2008). Also, it is also more
expressed in visceral than in
subcutaneous fat (Fain et al.,
2004; Einstein et al., 2005; Cao et
al., 2008; Maury et al., 2009).

- It is produced by macrophages,
endothelial cells and adipocytes
(Gerhardt et al., 2001; Christiansen
et al., 2005). It is more expressed in
stromal-vascular cells than in
adipocytes and in visceral adipose
tissue than in subcutaneous
adipose tissue (Bruun et al., 2005).

- Omental adipose tissue

produces more IL-6 than
adipose tissue, and IL-6
humans was significantly
greater than that released
adipocytes (Zhuang et al.,

Functions &

- The effects of TNF- on

adipocytes include inhibition of
lipogenesis, elevated lipolysis,
decreased adiponectin secretion,
reduced glucose transporter-4
expression, and impaired insulin
signaling (Moller, 2000; Trujillo et
al., 2006).

- It is a potent chemoattractant
playing a role in the recruitment of
(macrophage infiltration) into the
adipose tissue and lymphocyte
recruitment to sites of injury and
infection (Baggiolini, 1998; Maury
and Brichard, 2010).

- It not only acts in

paracrine/autocrine pathway
also acts
pathways to reduce the
extension of fat tissue.

- In general, TNF- also plays

important role in the development
of atherosclerosis through its
monocytetomacrophage conversion, at the
endothelial cell wall via nuclear

- MCP-1 may predominantly

produce local (autocrine/paracrine)
effects in adipose tissue rather than
having a direct systemic pathogenic

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factor kappa-light-chain-enhancer
of activated B-cells (NF-B)
activation, and in inflammatory
changes in the vascular wall
(Fonseca-Alaniz et al., 2007).
Activity &
in obesity &

- It is overexpressed in adipose
tissue of obese individuals (Maury
et al., 2009) and fall after weight
loss (Dandona et al., 1998). Its
elevation can reduce visceral fat
volume (Maury and Brichard,

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- Circulating and adipose tissue

levels of MCP-1 are elevated in
obese (Bruun et al., 2005) rodents
(Sartipy and Loskutoff, 2003;
Takahashi et al., 2003) and
individuals (Nomura et al., 2000;
Piemonti et al., 2003), and their
levels have been found to decrease
after weight-loss (Schernthaner et
al., 2006).

- Plasma IL6 levels are

elevated in obesity and in
T2DM and are positively
associated with plasma FFA
levels and with body mass
(Lazar, 2005; Urs et al.,
2004; Bastard et al., 2007)
where this can reduce
visceral fat volume (Maury
and Brichard, 2010).

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